Reducing maternal mortality in low- and middle-income countries: the Nepalese approach of helicopter retrieval.

Ninety-four percent of global maternal deaths occur in low- and middle-income countries (LMICs). The UN has a goal of reducing maternal deaths to <70 per 100,000 live births by 2030, but progress is minimal. Maternal deaths in LMICs are associated with 3 delays in the care of women with obstetrical emergencies: 1) in the family of the woman realizing that her life is at risk, 2) in the transport of the woman to a hospital, and 3) in providing care after arrival at the hospital. These 3 delays function like links in a chain, and failure of any link leads to maternal death. LMICs have characteristics that make it likely that the chain will break. Women in LMICs frequently have low standing, and cultural beliefs often lead to delay in the recognition of obstetrical emergencies. LMICs are characterized by poor roads and long distances to hospitals leading to transport delays. Cultural and other factors also lead to treatment delays when a woman reaches a suitably-equipped and staffed hospital. Nepal has addressed these delays and reduced maternal mortality. Firstly, we have reported in the Journal the use of culturally acceptable approaches to improving the knowledge about antenatal care in remote villages. In the case of Nepal, singing songs related to maternal care proved to be a highly effective strategy. We now report that the government of Nepal has repurposed military helicopters to overcome the tyranny of poor roads to allow rapid transport of women with obstetrical emergencies to a small number of fully-equipped and staffed hospitals. As of June 2023, this service has successfully retrieved 625 women in four and half years. The Nepalese government has included questions on maternal mortality in the 2021 national census, followed by a verbal autopsy. These data indicate a fall in the maternal mortality ratio from 239 in 2016 to 151 in 2021. The efficiency of the triage service continues to improve, suggesting that maternal mortality will continue to fall. This may provide a model that can be implemented in other LMICs and highlights factors that may be responsible for recent increases in the US maternal mortality ratio.

Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections.

Early initiation of antimicrobial therapy targeting resistant bacterial pathogens causing sepsis and bloodstream infections (BSIs) is critical for a successful outcome. The T2Resistance Panel (T2R) detects the following resistance genes within organisms that commonly cause BSIs directly from patient blood samples: blaKPC, blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, blaOXA, vanA, vanB, and mecA/mecC. We conducted a prospective study in two major medical centers for the detection of circulating resistance genes by T2R in patients with BSIs. T2R reports were compared to antimicrobial susceptibility testing (AST), phenotypic identification, and standard molecular detection assays. Among 59 enrolled patients, 25 resistance genes were identified: blaKPC (n = 10), blaNDM/bla/IMP/blaVIM (n = 5), blaCTXM-14/15 (n = 4), blaAmpC (n = 2), and mecA/mecC (n = 4). Median time-to-positive-T2R in both hospitals was 4.4 hours [interquartile range (IQR): 3.65-4.97 hours] in comparison to that for positive blood cultures with final reporting of AST of 58.34 h (IQR: 45.51-111.2 hours; P < 0.0001). The sensitivity of T2R to detect the following genes in comparison to AST was 100% for blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, mecA/mecC and 87.5% for blaKPC. When monitored for the impact of significant antimicrobial changes, there were 32 events of discontinuation of unnecessary antibiotics and 17 events of escalation of antibiotics, including initiation of ceftazidime/avibactam in six patients in response to positive T2R results for blaKPC. In summary, T2R markers were highly sensitive for the detection of drug resistance genes in patients with bacterial BSIs, when compared with standard molecular resistance detection systems and phenotypic identification assays while significantly reducing by approximately 90% the time to detection of resistance compared to standard methodology and impacting clinical decisions for antimicrobial therapy. IMPORTANCE: This is the first reported study to our knowledge to identify key bacterial resistance genes directly from the bloodstream within 3 to 5 hours in patients with bloodstream infections and sepsis. The study further demonstrated a direct effect in modifying initial empirical antibacterial therapy in response to T2R signal to treat resistant bacteria causing bloodstream infections and sepsis.

Sex-specific associations between placental corticotropin releasing hormone and problem behaviors in childhood.

Placental corticotropin-releasing hormone (pCRH) is a neuroactive peptide produced in high concentrations in mid-late pregnancy, during key periods of fetal brain development. Some evidence suggests that higher pCRH exposure during gestation is associated with adverse neurodevelopment, particularly in female offspring. In 858 mother-child dyads from the sociodemographically diverse CANDLE cohort (Memphis, TN), we examined: (1) the slope of pCRH rise in mid-late pregnancy and (2) estimated pCRH at delivery as a measure of cumulative prenatal exposure. When children were 4 years-old, mothers reported on problem behaviors using the Child Behavior Checklist (CBCL) and cognitive performance was assessed by trained psychologists using the Stanford-Binet Intelligence Scales. We fitted linear regression models examining pCRH in relation to behavioral and cognitive performance measures, adjusting for covariates. Using interaction models, we evaluated whether associations differed by fetal sex, breastfeeding, and postnatal neighborhood opportunity. In the full cohort, log-transformed pCRH measures were not associated with outcomes; however, we observed sex differences in some models (interaction p-values≤0.01). In male offspring, an interquartile (IQR) increase in pCRH slope (but not estimated pCRH at delivery), was positively associated with raw Total (ß=3.06, 95%CI: 0.40, 5.72), Internalizing (ß=0.89, 95%CI: 0.03, 1.76), and Externalizing (ß=1.25, 95%CI: 0.27, 2.22) Problem scores, whereas, in females, all associations were negative (Total Problems: ß=-1.99, 95%CI: -3.89, -0.09; Internalizing: ß=-0.82, 95%CI: -1.42, -0.23; Externalizing: ß=-0.56, 95%CI: -1.34, 0.22). No associations with cognitive performance were observed nor did we observe moderation by breastfeeding or postnatal neighborhood opportunity. Our results provide further evidence that prenatal pCRH exposure may impact subsequent child behavior in sex-specific ways, however in contrast to prior studies suggesting adverse impacts in females, steeper mid-gestation pCRH rise was associated with more problem behaviors in males, but fewer in females.

Effectiveness and cost-effectiveness of online recorded recovery narratives in improving quality of life for people with non-psychotic mental health problems: a pragmatic randomized controlled trial.

Narratives describing first-hand experiences of recovery from mental health problems are widely available. Emerging evidence suggests that engaging with mental health recovery narratives can benefit people experiencing mental health problems, but no randomized controlled trial has been conducted as yet. We developed the Narrative Experiences Online (NEON) Intervention, a web application providing self-guided and recommender systems access to a collection of recorded mental health recovery narratives (n=659). We investigated whether NEON Intervention access benefited adults experiencing non-psychotic mental health problems by conducting a pragmatic parallel-group randomized trial, with usual care as control condition. The primary endpoint was quality of life at week 52 assessed by the Manchester Short Assessment (MANSA). Secondary outcomes were psychological distress, hope, self-efficacy, and meaning in life at week 52. Between March 9, 2020 and March 26, 2021, we recruited 1,023 participants from across England (the target based on power analysis was 994), of whom 827 (80.8%) identified as White British, 811 (79.3%) were female, 586 (57.3%) were employed, and 272 (26.6%) were unemployed. Their mean age was 38.4±13.6 years. Mood and/or anxiety disorders (N=626, 61.2%) and stress-related disorders (N=152, 14.9%) were the most common mental health problems. At week 52, our intention-to-treat analysis found a significant baseline-adjusted difference of 0.13 (95% CI: 0.01-0.26, p=0.041) in the MANSA score between the intervention and control groups, corresponding to a mean change of 1.56 scale points per participant, which indicates that the intervention increased quality of life. We also detected a significant baseline-adjusted difference of 0.22 (95% CI: 0.05-0.40, p=0.014) between the groups in the score on the "presence of meaning" subscale of the Meaning in Life Questionnaire, corresponding to a mean change of 1.1 scale points per participant. We found an incremental gain of 0.0142 quality-adjusted life years (QALYs) (95% credible interval: 0.0059 to 0.0226) and a £178 incremental increase in cost (95% credible interval: -£154 to £455) per participant, generating an incremental cost-effectiveness ratio of £12,526 per QALY compared with usual care. This was lower than the £20,000 per QALY threshold used by the National Health Service in England, indicating that the intervention would be a cost-effective use of health service resources. In the subgroup analysis including participants who had used specialist mental health services at baseline, the intervention both reduced cost (-£98, 95% credible interval: -£606 to £309) and improved QALYs (0.0165, 95% credible interval: 0.0057 to 0.0273) per participant as compared to usual care. We conclude that the NEON Intervention is an effective and cost-effective new intervention for people experiencing non-psychotic mental health problems.

Sirenomelia: An anatomical assessment and genetic sex determination of two cases.

The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular genetic analysis. The purpose of the current study was designed to compare external and internal anatomical defects in two cases of sirenomelia and Potter's sequence. Considered rare, Potter's sequence is a fetal disorder with characteristic features of bilateral renal agenesis, obstructive uropathy, atypical facial appearance, and limb malformations. The internal and external malformations of two term fetuses with sirenomelia and Potter's sequence were compared using assessment of external features, radiography and MRI on internal structures, and molecular genetic studies on sex determination. Data reveal that both fetuses were male and manifested with an overlapping but distinct spectrum of abnormalities. Principal differences were noted in the development of the ears, brain, urogenital system, lower limbs, pelvis, and vertebral column. Defects of the axial mesoderm are likely to underlie the abnormalities seen in both fetuses. The first one, which had only caudal defects, was found to have a spectrum of abnormalities most similar to those associated with more severe forms of the small pelvic outlet syndrome, although the structure and orientation of the sacrum and iliae were different from previously reported cases. The other had both caudal and cranial defects, and was most similar to those described in the axial mesodermal dysplasia syndrome. Defects associated with sirenomelia can be evaluated with standard gross anatomy examination, radiology, MRI, and modified PCR techniques to determine anatomical abnormalities and the sex of preserved specimens, respectively. Evidence indicated that sirenomelia could be developed via various etiologies.

Human placenta releases extracellular vesicles carrying corticotrophin releasing hormone mRNA into the maternal blood.

The human placenta releases diverse extracellular vesicles (EVs), including microvesicles (100-1000 nm) and exosomes (30-150 nm), into the maternal blood for feto-maternal communication. Exosomes and microvesicles contribute to normal pregnancy physiology and major pregnancy pathologies. Differences in miRNA expressions and protein content in placental exosomes have been reported in complicated pregnancies. During human pregnancy, Corticotropin-Releasing Hormone (CRH) is produced and released by the placenta into the maternal blood. CRH is involved in regulating gestational length and the initiation of labour. CRH mRNA levels in the maternal plasma rise with gestation. High levels of CRH mRNA are reported to be associated with preeclamptic and preterm pregnancies. However, the underlying mechanism of placental CRH mRNA secretion remains to be elucidated. We hypothesise that the placenta releases CRH mRNA packaged within extracellular vesicles (EVs) into the maternal blood. In this study, placental EVs (microvesicles and exosomes) were isolated from human term healthy placentas via villus washes and from explant culture media by differential centrifugation and purified by density gradient ultracentrifugation using a continuous sucrose gradient (0.25-2.5 M). Western blotting using placenta- and exosome-specific markers and electron microscopy confirmed exosomes and microvesicles in the placental wash and explant media samples. Real-time quantitative RT-PCR data detected CRH mRNA in placenta-derived EVs from placental washes and explants. We also sorted placenta-secreted EVs in maternal plasma samples (≥37 weeks) by high-resolution flow cytometry using a fluorescent-labelled PLAP antibody. CRH mRNA was demonstrated in placental EVs obtained from maternal blood plasma. We therefore show that human placental EVs carry CRH mRNA into the maternal blood. Our study implies that measuring CRH mRNA in placental EVs in the maternal plasma could beused for monitoring pregnancy.

Regulation of 20α-Hydroxysteroid Dehydrogenase Expression in Term Pregnant Human Myometrium Ex Vivo.

Metabolic inactivation of progesterone within uterine myocytes by 20α-hydroxysteroid dehydrogenase (20α-HSD) has been postulated as a mechanism contributing to functional progesterone withdrawal at term. In humans, 20α-HSD is encoded by the gene AKR1C1. Myometrial AKR1C1 mRNA abundance has been reported to increase significantly during labor at term. In spontaneous preterm labor, however, we previously found no increase in AKR1C1 mRNA level in the myometrium except for preterm labor associated with clinical chorioamnionitis. This suggests that increased 20α-HSD activity is a mechanism through which inflammation drives progesterone withdrawal in preterm labor. In this study, we have determined the effects of various treatments of therapeutic relevance on AKR1C1 expression in pregnant human myometrium in an ex vivo culture system. AKR1C1 expression increased spontaneously during 48 h culture (p < 0.0001), consistent with the myometrium transitioning to a labor-like phenotype ex vivo, as reported previously. Serum supplementation, prostaglandin F2α, phorbol myristate acetate, and mechanical stretch had no effect on the culture-induced increase, whereas progesterone (p = 0.0058) and cAMP (p = 0.0202) further upregulated AKR1C1 expression. In contrast, culture-induced upregulation of AKR1C1 expression was dose-dependently repressed by three histone/protein deacetylase inhibitors: trichostatin A at 5 (p = 0.0172) and 25 µM (p = 0.0115); suberoylanilide hydroxamic acid at 0.5 (p = 0.0070), 1 (p = 0.0045), 2.5 (p = 0.0181), 5 (p = 0.0066) and 25 µM (p = 0.0014); and suberoyl bis-hydroxamic acid at 5 (p = 0.0480) and 25 µM (p = 0.0238). We propose the inhibition of histone/protein deacetylation helps to maintain the anti-inflammatory, pro-quiescence signaling of progesterone in pregnant human myometrium by blocking its metabolic inactivation. Histone deacetylase inhibitors may represent a class of agents that preserve or restore the progesterone sensitivity of the pregnant uterus.

Countermovement Jump Force-Time Curve Analyses: Reliability and Comparability Across Force Plate Systems.

ABSTRACT: Merrigan, JJ, Strang, A, Eckerle, J, Mackowski, N, Hierholzer, K, Ray, NT, Smith, R, Hagen, JA, and Briggs, RA. Countermovement jump force-time curve analyses: reliability and comparability across force plate systems. J Strength Cond Res 38(1): 30-37, 2024-Considering the growing prevalence of commercial force plates providing automated force-time analyses, understanding levels of agreement across force plate systems is warranted. Countermovement jump (CMJ) metrics across Vald ForceDecks (FD), Hawkin Dynamics (HD), and Sparta Science (SS) force plate systems were compared. Twenty-two subjects completed CMJ testing (∼128 comparisons) on each force plate system separately with rest between jumps. Baseline testing occurred 3 times and demonstrated poor test-retest reliability for modified reactive strength index (mRSI) and rate of force development (RFD). ForceDecks and HD comparisons yielded acceptable agreement for concentric/propulsive relative force and net impulse, jump height, eccentric/braking RFD, and mRSI, but systematic and proportionate bias existed for RFD. Sparta Science jump height and reactive strength index (RSI) demonstrated systematic overestimations compared with HD and FD, but jump height had acceptable agreement according to concordance correlation coefficients (CCC = 0.92-0.95). Agreement between SS load (eccentric RFD) and HD braking RFD was acceptable (CCC = 0.91), whereas agreement between SS load and FD deceleration RFD was considered acceptable (CCC = 0.81-0.87) but demonstrated systematic and proportionate bias. ForceDecks (CCC = 0.89) and HD (CCC = 0.85) average relative concentric/propulsive force yielded acceptable agreement with SS explode (average relative concentric force), but SS explode demonstrated systematically lower values than FD and HD. Sparta Science drive (concentric impulse) yielded acceptable agreement with HD relative propulsive impulse (CCC = 0.85), but not FD concentric impulse. Human performance practitioners need to be aware of inconsistencies among testing procedures and analyses across force plate systems, such as differences in metric definitions and units of measurement, before making comparisons across systems.

Changes in Head and Pelvic Movement Symmetry after Diagnostic Anaesthesia: Interactions between Subjective Judgement Categories and Commonly Applied Blocks.

Limited evidence is available relating gait changes to diagnostic anaesthesia. We investigated associations between specific movement patterns and diagnostic anaesthesia of different anatomical structures in a retrospective analysis. Referral-level lameness cases were included with the following criteria: presence of diagnostic anaesthesia of a forelimb and/or hind limb; subjective efficacy classified as "negative", "partially positive", or "positive"; quantitative gait data available from inertial measurement units. Gait changes were calculated for three forelimb (palmar digital, abaxial sesamoid, low 4-point nerve block) and five hind limb diagnostic blocks (tarso-metatarsal, metatarsophalangeal joint block, deep branch of lateral plantar, low 6-point, abaxial sesamoid nerve block). Mixed models (random factor "case", fixed factors "diagnostic anaesthesia type" and "efficacy", two-way interaction) assessed the head and pelvic movement (p < 0.05, Bonferroni correction). Four parameters were significantly affected by forelimb anaesthesia (N = 265) (all p ≤ 0.031) and six by hind limb anaesthesia (N = 342) efficacy (all p ≤ 0.001). All head movement parameters and pelvic push-off asymmetry were significantly affected by the two-way interaction after forelimb anaesthesia (all p ≤ 0.023) and two pelvic movement symmetry parameters by the two-way interaction after hind limb anaesthesia (all p ≤ 0.020). There are interactions between block efficacy and type resulting in changes in weight-bearing and push-off-associated head and pelvic movement symmetry after diagnostic anaesthesia.

Widespread BRCA1/2-independent homologous recombination defects are caused by alterations in RNA-binding proteins.

Defects in homologous recombination DNA repair (HRD) both predispose to cancer development and produce therapeutic vulnerabilities, making it critical to define the spectrum of genetic events that cause HRD. However, we found that mutations in BRCA1/2 and other canonical HR genes only identified 10%-20% of tumors that display genomic evidence of HRD. Using a networks-based approach, we discovered that over half of putative genes causing HRD originated outside of canonical DNA damage response genes, with a particular enrichment for RNA-binding protein (RBP)-encoding genes. These putative drivers of HRD were experimentally validated, cross-validated in an independent cohort, and enriched in cancer-associated genome-wide association study loci. Mechanistic studies indicate that some RBPs are recruited to sites of DNA damage to facilitate repair, whereas others control the expression of canonical HR genes. Overall, this study greatly expands the repertoire of known drivers of HRD, with implications for basic biology, genetic screening, and therapy stratification.

Effects of resveratrol and its analogues on the cell cycle of equine mesenchymal stem/stromal cells.

Resveratrol (RSV; trans-3,5,4'-trihydroxystilbene) strongly activates sirtuin 1, and it and its analogue V29 enhance the proliferation of mesenchymal stem/stromal cells (MSCs).Although culture medium containing 5-azacytydine and RSV inhibits senescence of adipose tissue-derived MSCs isolated from horses with metabolic syndrome, few studies have reported the effects of RSV on equine bone marrow-derived MSCs (eBMMSCs) isolated from horses without metabolic syndrome. The aim of this study was to investigate the effects of RSV and V29 on the cell cycle of eBMMSCs. Following treatment with 5 µM RSV or 10 µM V29, the cell proliferation capacity of eBMMSCs derived from seven horses was evaluated by EdU (5-ethynyl-2'-deoxyuridine) and Ki-67 antibody assays. Brightfield images of cells and immunofluorescent images of EdU, Ki-67, and DAPI staining were recorded by fluorescence microscopy, and the number of cells positive for each was quantified and compared by Friedman's test at P<0.05. The growth fraction of eBMMSCs was significantly increased by RSV and V29 as measured by the EdU assay (control 28.1% ± 13.8%, V29 31.8% ± 14.6%, RSV 32.0% ± 10.8%; mean ± SD; P<0.05) but not as measured by the Ki-67 antibody assay (control 27.0% ± 11.2%, V29 27.4% ± 10.8%, RSV 27.7% ± 6.8%). RSV and V29 promoted progression of the cell cycle of eBMMSCs into the S phase and may be useful for eBMMSC expansion.

Desmitis of the accessory ligament of the deep digital flexor tendon in the forelimb: A retrospective case study of 91 horses.

BACKGROUND: Desmitis of the accessory ligament of the deep digital flexor tendon (ALDDFT) is a commonly reported injury. Despite the commonality of this injury, the literature is limited to small case series, with the reported success following treatment varying from 18% to 75%. OBJECTIVES: To identify the prognosis and factors associated with a return to work following ALDDFT injury. STUDY DESIGN: Retrospective case series. METHODS: Medical records of horses from four equine hospitals (January 2000 and December 2018) with a diagnosis of desmitis of ALDDFT were reviewed. Data retrieved included case detail, use, history, lameness treatment and follow-up. Success was defined as returning to work. Backward stepwise logistic regression was used to identify variables significantly associated with return to work. RESULTS: Ninety-one horses were included. The mean age was 13.5 years (standard deviation 4.9 years). Thirty-four percent (28/91) of horses were sound at the initial presentation. Sixty-eight percent (62/91) of horses were managed using controlled exercise alone, 28% (29/91) were treated with intra-lesional injection, therapeutic ultrasound, extracorporeal shockwave therapy or desmectomy of the ALDDFT and 3% (3/91) were euthanased without treatment. Sixty-four percent (54/85) of horses returned to work. Horses that were lame at follow-up were less likely to return to work (odds ratio [OR] 107.93, 95% confidence interval [CI] 20.06-580.61, p < 0.001) than those that returned to soundness. Identification of adhesions on ultrasonography was also associated with having reduced odds for return to work when compared to horses without adhesions (OR 0.10, 95% CI 0.01-0.76, p = 0.03). MAIN LIMITATIONS: Retrospective nature of the study, the potential of selection bias with regards to follow-up. CONCLUSION: Sixty-four percent (54/85) of horses returned to work following injury of the ALDDFT. Persistence of lameness and adhesion formation were significantly associated with a poor outcome.

Does the Micronutrient Molybdenum Have a Role in Gestational Complications and Placental Health?

Molybdenum is an essential trace element for human health and survival, with molybdenum-containing enzymes catalysing multiple reactions in the metabolism of purines, aldehydes, and sulfur-containing amino acids. Recommended daily intakes vary globally, with molybdenum primarily sourced through the diet, and supplementation is not common. Although the benefits of molybdenum as an anti-diabetic and antioxidant inducer have been reported in the literature, there are conflicting data on the benefits of molybdenum for chronic diseases. Overexposure and deficiency can result in adverse health outcomes and mortality, although physiological doses remain largely unexplored in relation to human health. The lack of knowledge surrounding molybdenum intake and the role it plays in physiology is compounded during pregnancy. As pregnancy progresses, micronutrient demand increases, and diet is an established factor in programming gestational outcomes and maternal health. This review summarises the current literature concerning varied recommendations on molybdenum intake, the role of molybdenum and molybdoenzymes in physiology, and the contribution these play in gestational outcomes.

Retrospective Use of Patients' Characteristics to Assess Variation in Prenatal Care Utilization.

OBJECTIVE: We used patients' medical and psychosocial risk factors to explore prenatal care utilization and health outcomes to inform prenatal care tailoring. STUDY DESIGN: This retrospective cohort study assessed patients who gave birth at an academic institution from January 1 to December 31, 2018, using electronic health record (EHR) data. Patients were categorized into four phenotypes based on medical/psychosocial risk factors available in the EHR: Completely low risk; High psychosocial risk only; High medical risk only; and Completely high risk. We examined patient characteristics, visit utilization, nonvisit utilization (e.g., phone calls), and outcomes (e.g., preterm birth, preeclampsia) across groups. RESULTS: Of 4,681 patients, the majority were age 18 to 35 (3,697, 79.0%), White (3,326, 70.9%), multiparous (3,263, 69.7%), and Completely high risk (2,752, 58.8%). More Black and Hispanic patients had psychosocial risk factors than White patients. Patients with psychosocial risk factors had fewer prenatal visits (10, interquartile range [IQR]: 8-12) than those without (11, IQR: 9-12). Patients with psychosocial risk factors experienced less time in prenatal care, more phone calls, and fewer EHR messages across the same medical risk group. Rates of preterm birth and gestational hypertension were incrementally higher with additional medical/psychosocial risk factors. CONCLUSION: Data readily available in the EHR can assess the compounding influence of medical/psychosocial risk factor on patients' care utilization and outcomes. KEY POINTS: · Medical and psychosocial needs in pregnancy can inform patient phenotypes and are associated with prenatal care use and outcomes.. · Patient phenotypes are associated with prenatal care use and outcomes.. · Patients with high psychosocial risk spent less time in prenatal care and had more phone calls in pregnancy.. · Tailored prenatal care models may proactively address differences in patient's needs..

Extracellular vesicles- crucial players in human pregnancy.

Extracellular vesicles (EVs) are lipid-bilayer enclosed membrane vesicles released by cells in physiological and pathological states. EVs are generated and released through a variety of pathways and mediate cellular communication by carrying and transferring signals to recipient cells. EVs are specifically loaded with proteins, nucleic acids (RNAs and DNA), enzymes and lipids, and carry a range of surface proteins and adhesion molecules. EVs contribute to intercellular signalling, development, metabolism, tissue homeostasis, antigen presentation, gene expression and immune regulation. EVs have been categorised into three different subgroups based on their size: exosomes (30-150 nm), microvesicles (100-1000 nm) and apoptotic bodies (1-5 µm). The status of the cells of origin of EVs influences their biology, heterogeneity and functions. EVs, especially exosomes, have been studied for their potential roles in feto-maternal communication and impacts on normal pregnancy and pregnancy disorders. This review presents an overview of EVs, emphasising exosomes and microvesicles in a general context, and then focusing on the roles of EVs in human pregnancy and their potential as diagnostics for adverse pregnancy outcomes.

The postcranial anatomy of Gorgonops torvus (Synapsida, Gorgonopsia) from the late Permian of South Africa.

Gorgonopsians are among the most recognizable groups of synapsids from the Permian period and have an extensive but mostly cranial fossil record. By contrast, relatively little is known about their postcranial anatomy. Here, we describe a nearly complete, semi-articulated skeleton of a gorgonopsian (identified as Gorgonops torvus) from the late Permian Endothiodon Assemblage Zone of the South African Karoo Basin and discuss its paleobiological implications. Known gorgonopsian postcrania indicate morphological conservatism in the group, but the skeletal anatomy of Gorgonops does differ from that of other gorgonopsians in some respects, such as in the triangular radiale and short terminal phalanges in the manus, and a weakly developed distinction between pubis and ischium in ventral aspect of the pelvic girdle. Similarities between the specimen described herein and a historically problematic specimen originally referred to "Scymnognathus cf. whaitsi" confirm referral of the latter specimen to Gorgonops. Since descriptions of gorgonopsian postcrania are rare, new interpretations of the lifestyle and ecology of Gorgonopsia can be drawn from our contribution. We conclude that gorgonopsians were likely ambush predators, able to chase their prey over short distances and pin them down with strong forelimbs before using their canines for the kill. This is evidenced by their different fore- and hindlimb morphology; the former stouter and more robust in comparison to the longer, more gracile, back legs. Furthermore, the completeness of the study specimen facilitates calculation of an estimated body mass of approximately 98 kg, similar to that of a modern lioness.

Newcastle 1000 (NEW1000) Study: an Australian population-based prospective pregnancy cohort study design and protocol.

INTRODUCTION: Multiple cohort studies have been established to investigate the impact of early life factors on development and health outcomes. In Australia the majority of these studies were established more than 20 years ago and, although longitudinal in nature, are inherently susceptible to socioeconomic, environmental and cultural influences which change over time. Additionally, rapid leaps in technology have increased our understanding of the complex role of gene-environment interactions in life course health, highlighting the need for new cohort studies with repeated biological sampling and in-depth phenotype data across the first 1000 days of life from conception. METHODS AND ANALYSIS: The Newcastle 1000 (NEW1000) Study, based in the regional city of Newcastle, New South Wales, was developed after an extensive consultation process involving 3 years of discussion with key stakeholders and healthcare consumer organisations and seven healthcare consumer workshops. This prospective population-based pregnancy cohort study will recruit 500 families per year for 5 years, providing detailed, longitudinal, multisystem phenotyping, repeated ultrasound measures and serial sample collection to investigate healthcare consumer identified health outcomes of priority. Stage 1 will involve recruitment of pregnant participants and their partners at 14 weeks gestation, with dense phenotype data and biological samples collected at 14, 20, 28 and 36 weeks gestation and serial ultrasound measures at 20, 28, 36 and 40 weeks, with postpartum follow-up at 6 weeks and 6 months. Biological samples will be used for biomarker discovery and sequencing of the genome, transcriptome, epigenome, microbiome and metabolome. ETHICS AND DISSEMINATION: Ethics approval was obtained from Hunter New England Local Health District Ethics Committee (2020/ETH02881). Outcomes will be published in peer-reviewed journals, disseminated to participants through the NEW1000 website, presented at scientific conferences, and written reports to local, state and national government bodies and key stakeholders in the healthcare system to inform policy and evidence-based practice.

Tubal Sterilization Requests at a Single Institution Following the Supreme Court Decision to Overturn the Constitutional Right to Abortion.

This study uses data from electronic health records to examine the rate of tubal sterilization requests in 3 periods before and after the US Supreme Court's 2022 Dobbs v Jackson Women's Health Organization decision, compared with the same periods in 2019 and 2021, at a single institution in Michigan.